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Material and methods
Results
Discussion
It is challenging to discriminate between HIV monoinfection and HIV-1/2 dual infection in settings where both viruses co-exist, due to cross-reactivity in serological tests. Thus, the gold standard for detection of HIV-1/2 dual infection is through NAAT. These procedures are however not generally available in resource-limited settings and consequently it is important to have as accurate serological tests as possible. Recently a point-of-care molecular test (Alere q HIV-1/2 Detect, Alere Detect) for HIV-1 and HIV-2 RNA detection was evaluated and the authors concluded that this test is a potential diagnostic tool in resource limited settings (Chang et al., 2017).
Previous studies (Andersson et al., 1997; Walther-Jallow et al., 1999; Gautheret-Dejean et al., 2015) have found that Immunocomb to some degree overestimates the number of HIV-1/2 dually reactive results but not reaching the extent seen in our material. This is most likely due to inter-reader variability which have been reported previously (Hønge et al., 2018). In Ac-IETD-AFC australia we had two independent observers reading Geenius according to the inlet instructions with full agreement. Misclassification of HIV-2 and HIV-1/2 dual reaction fortunately has no implication on ART regimen selection with current drug regimens but could have personal implications as HIV-1/2 dually infected individuals progress faster to AIDS than HIV-2 infected individuals (Esbjornsson et al., 2012; Esbjörnsson et al., 2014). Geenius performs considerably better than Immunocomb and both the Geenius reader and manual reading of Geenius showed good concordance with INNO-LIA.
The findings in this study are subject to several limitations. First and foremost it was not designed as a complete sensitivity and specificity assessment of the Geenius assay. In 37.8–41.7% of samples typed as HIV-2 positive by INNO-LIA and the different Geenius reading options HIV-2 RNA could not be detected which however is consistent with previous findings where undetectable HIV-2 RNA levels has been reported in 36–46% of ART naïve HIV-2 patients (Gottlieb et al., 2002; Chang et al., 2012; Ekouevi et al., 2015). Samples from some patients classified as HIV-1/2 dually reactive by Geenius and INNO-LIA could not be confirmed by RNA/DNA analyses. This could be due to suppression of the less dominant HIV type (Raugi et al., 2013). The low proportion of samples with confirmed HIV DNA could be due to low leukocyte number and consequently low concentration of DNA in our material, but unfortunately information on cell count was not available. The use of digital droplet PCR might have been more sensitive for HIV DNA leading to more HIV-1/2 dually reactive samples being confirmed. Another possibility would be misclassification by INNO-LIA and Geenius.
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Introduction
Significantly improved combined antiretroviral treatment (cART) and progress in the management of human immunodeficiency virus-1 (HIV-1) infection changed the clinical course of HIV-infection to a chronic disease with approximately normal life-expectancy. The reconstitution of the immune system and a decreased rate of HIV-associated diseases have greatly reduced mortality among HIV-infected patients [1]. Cardiovascular disease (CVD) is now one of the leading causes of morbidity and mortality in countries with established cART [2,3]. Individuals with HIV have higher rates of CVD than uninfected subjects [4], likely because of a combination of traditional CV risk factors as well as independent effects of HIV itself such as inflammatory and immunologic factors and toxicities of cART [5,6]. The longer life expectancy of HIV-infected populations due to a reduced death rate of HIV-specific causes after the introduction of cART coupled with the increased risk for CVD makes CV risk assessment an important part of HIV care. However, CV risk stratification remains a challenge in HIV-infected subjects. The accuracy of established CVD risk prediction underestimates the observed incidence of cardiovascular events and diseases [7]. Brain natriuretic peptide (BNP) is one of the important biomarkers with a proven role in the diagnosis of congestive heart failure [8,9] and has recently been associated with CV disease and all-cause mortality in patients even without known CV disease [[10], [11], [12]]. The potency of BNP has also been researched in myocardial ischemia, cor pulmonale and acute pulmonary embolism [13]. However, the prognostic utility to predict CV events and mortality in HIV-infected patients is still unclear. Therefore, the aim of this study was to assess, whether BNP improves risk prediction of CV events and mortality in a German cohort of HIV-positive subjects in the HIV-HEART study.